The developmental mutants of Drosophila melanogaster have been a rich and productive source for investigations into basic mechanisms of development. Indeed, the explosive progress in our understanding of the molecular events in early Drosophila embryogenesis already justified the extensive investments in basic genetic and developmental studies that have provided the requisite materials and conceptual foundation. This progress also justifies our optimism that the Drosophila system will continue to provide valuable insights. We have chosen to intensively study one such locus in Drosophila, engrailed. Studies of mutants indicate that the engrailed function is essential during the precellular stages of embryogenesis for the formation of the blastoderm, during the gastrulation period for normal segmentation, and throughout subsequent development for maintenance of the segmental and compartmental subdivisions. The gene has been cloned, the gene structure and transcription unit has been defined, and the engrailed protein has been isolated. This system is now poised for molecular and enzymological studies to establish how the gene is regulated to effects to precise a program of positional and temporal expression, and to determine how the engrailed protein performs its several roles. We will approach these goals by: (1) isolating cis and trans acting mutations that affect the regulation of the engrailed gene; (2) analyzing the cis regulatory elements of the engrailed promoter by DNA transformation, and by isolating and characterizing the enzymes that regulate transcription of the engrailed gene; and (3) studying the activities and behavior of the engrailed protein.